Published Online October 9, 2019 ; Gesehen am 15.04.2020
Background - Further improvement of preparative regimens before allogeneic haemopoietic stem cell transplantation (HSCT) is an unmet medical need for the growing number of older or comorbid patients with acute myeloid leukaemia or myelodysplastic syndrome. We aimed to evaluate the efficacy and safety of conditioning with treosulfan plus fludarabine compared with reduced-intensity busulfan plus fludarabine in this population. - Methods - We did an open-label, randomised, non-inferiority, phase 3 trial in 31 transplantation centres in France, Germany, Hungary, Italy, and Poland. Eligible patients were 18-70 years, had acute myeloid leukaemia in first or consecutive complete haematological remission (blast counts <5% in bone marrow) or myelodysplastic syndrome (blast counts <20% in bone marrow), Karnofsky index of 60% or higher, and were indicated for allogeneic HSCT but considered at an increased risk for standard myeloablative preparative regimens based on age (≥50 years), an HSCT-specific comorbidity index of more than 2, or both. Patients were randomly assigned (1:1) to receive either intravenous 10 g/m2 treosulfan daily applied as a 2-h infusion for 3 days (days -4 to -2) or 0·8 mg/kg busulfan applied as a 2-h infusion at 6-h intervals on days -4 and -3. Both groups received 30 mg/m2 intravenous fludarabine daily for 5 days (days -6 to -2). The primary outcome was event-free survival 2 years after HSCT. The non-inferiority margin was a hazard ratio (HR) of 1·3. Efficacy was assessed in all patients who received treatment and completed transplantation, and safety in all patients who received treatment. The study is registered with EudraCT (2008-002356-18) and ClinicalTrials.gov (NCT00822393). - Findings - Between June 13, 2013, and May 3, 2016, 476 patients were enrolled (240 in the busulfan group received treatment and transplantation, and in the treosulfan group 221 received treatment and 220 transplanation). At the second preplanned interim analysis (Nov 9, 2016), the primary endpoint was met and trial was stopped. Here we present the final confirmatory analysis (data cutoff May 31, 2017). Median follow-up was 15·4 months (IQR 8·8-23·6) for patients treated with treosulfan and 17·4 months (6·3-23·4) for those treated with busulfan. 2-year event-free survival was 64·0% (95% CI 56·0-70·9) in the treosulfan group and 50·4% (42·8-57·5) in the busulfan group (HR 0·65 [95% CI 0·47-0·90]; p<0·0001 for non-inferiority, p=0·0051 for superiority). The most frequently reported grade 3 or higher adverse events were abnormal blood chemistry results (33 [15%] of 221 patients in the treosulfan group vs 35 [15%] of 240 patients in the busulfan group) and gastrointestinal disorders (24 [11%] patients vs 39 [16%] patients). Serious adverse events were reported for 18 (8%) patients in the treosulfan group and 17 (7%) patients in the busulfan group. Causes of deaths were generally transplantation-related. - Interpretation - Treosulfan was non-inferior to busulfan when used in combination with fludarabine as a conditioning regimen for allogeneic HSCT for older or comorbid patients with acute myeloid leukaemia or myelodysplastic syndrome. The improved outcomes in patients treated with the treosulfan-fludarabine regimen suggest its potential to become a standard preparative regimen in this population. - Funding - medac GmbH.
The lancet. Haematology London [u.a.] : Elsevier, 2014 7(2020), 1, Seite e28-e39 Online-Ressource
von Miriam Seifert ; Jan M. Hoppema ; Claudia Burau ; Cassandra Elmer ; Anna Friedrichs ; Jana K. Geuer ; Uwe John ; Torsten Kanzow ; Boris P. Koch ; Christian Konrad ; Helga van der Jagt ; Oliver Zielinski ; Morten Hvitfeldt Iversen
von Boris Koch ; Uwe John ; Rudi Amann ; Philipp Assmy ; Lennart Bach ; Claudia Burau ; Bente Edvardsen ; Mar Fernandez-Mendez ; Anna Friedrichs ; Jana Geuer ; Mario Hoppema ; Oliver Huhn ; Morten Iversen ; Christian Konrad ; Nancy Kühne ; Oliver Lechtenfeld ; Andreas Mackensen ; S. Leigh McCallister ; Elina Nystedt ; Philippe Schmidt-Kopplin ; Kai Schwalfenberg ; Miriam Seifert ; Colin Stedmon ; Dedmer van de Waal ; Helga van der Jagt ; Sylke Wohlrab ; Jörg Wulf ; Urban Wünsch ; Oliver Zielinski
von Julia A. Busch ; Raul Bardaji ; Luigi Ceccaroni ; Anna Friedrichs ; Jaume Piera ; Carine Simon ; Peter Thijsse ; Marcel Wernand ; Hendrik J. van der Woerd ; Oliver Zielinski
von Anna Bergstermann ; Eva Cendon ; Luise B. Flacke ; Andreas Friedrich ; Christine Hiltergerke ; Miriam Schäfer ; Sabrina Strazny ; Fabienne Theis ; Nina Maria Wachendorf ; Kathrin Wetzel
Bonn Berlin: Bundesministerium für Bildung und Forschung
46 Seiten.
Literaturverzeichnis: Seite 40-43
Handreichung Lernergebnisse / herausgegeben durch: die wissenschaftliche Begleitung des Bund-Länder-Wettbewerbs "Aufstieg durch Bildung: offene Hochschulen", vertreten durch die Projektleitungen: Prof. Dr. Anke Hanft (Carl von Ossietzky Universität Oldenburg), Prof. Dr. Andrä Wolter (Humboldt-Universität zu Berlin), Prof. Dr. Ada Pellert (Deutsche Universität für Weiterbildung), Dr. Eva Cendon (Deutsche Universität für Weiterbildung)Handreichung der wissenschaftlichen Begleitung des Bund-Länder-Wettbewerbs "Aufstieg durch Bildung: offene Hochschulen"
Handreichung Lernergebnisse / herausgegeben durch: die wissenschaftliche Begleitung des Bund-Länder-Wettbewerbs "Aufstieg durch Bildung: offene Hochschulen", vertreten durch die Projektleitungen: Prof. Dr. Anke Hanft (Carl von Ossietzky Universität Oldenburg), Prof. Dr. Andrä Wolter (Humboldt-Universität zu Berlin), Prof. Dr. Ada Pellert (Deutsche Universität für Weiterbildung), Dr. Eva Cendon (Deutsche Universität für Weiterbildung) ; Teil 1;
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